Homeyer Marie A, Falck Alice, Li Lucie Y, Prüss Harald
Charité - Universitätsmedizin Berlin, Berlin, Germany.
Charité - Universitätsmedizin Berlin, Berlin, Germany.
Semin Immunol. 2025 Jun;78:101955. doi: 10.1016/j.smim.2025.101955. Epub 2025 Apr 22.
Autoimmune encephalitides (AEs) are neurological disorders caused by autoantibodies against neuronal and glial surface proteins. Nearly 20 years after their discovery, AE have evolved from being frequently misdiagnosed and untreated to a growing group of increasingly well-characterized conditions where patients benefit from targeted therapeutic strategies. This narrative review provides an immunological perspective on AE, focusing on NMDAR, CASPR2 and LGI1 encephalitis as the three most common forms of AE associated with anti-neuronal surface autoantibodies. We examine the autoreactive B cell subsets, the tolerance checkpoints that may fail, and the known triggers and predispositions contributing to disease. In addition, we discuss the roles of other immune cells, including T cells and microglia, in the pathogenesis of AE. By analyzing therapeutic strategies and treatment responses we draw insights into AE pathophysiology. Written at a time of transformative therapeutic advancements through cell therapies this work underscores the synergy between detailed immunological research and the development of innovative therapies.
自身免疫性脑炎(AE)是由针对神经元和神经胶质表面蛋白的自身抗体引起的神经系统疾病。在其被发现近20年后,AE已从经常被误诊和未得到治疗发展为一类特征日益明确的疾病,患者可从靶向治疗策略中获益。这篇叙述性综述从免疫学角度对AE进行了阐述,重点关注NMDAR、CASPR2和LGI1脑炎这三种与抗神经元表面自身抗体相关的最常见AE形式。我们研究了自身反应性B细胞亚群、可能失效的耐受性检查点以及导致疾病的已知触发因素和易患因素。此外,我们还讨论了包括T细胞和小胶质细胞在内的其他免疫细胞在AE发病机制中的作用。通过分析治疗策略和治疗反应,我们深入了解了AE的病理生理学。在通过细胞疗法实现治疗变革性进展的时代撰写本文,强调了详细的免疫学研究与创新疗法开发之间的协同作用。